A new biomarker for frontotemporal lobar degeneration with TDP-43 proteinopathy and Alzheimer's Disease

In this grant application the PI (Qinwen Mao, Univ. of Utah) proposes to study the role of TAR DNA binding protein of 43 kDa (TDP-43) that was first associated with frontotemporal lobar degeneration (FTLD)—the second most common cause of dementia in patients <65. More recently, TDP-43 pathology has been found in up to 60% of brains with Alzheimer’s disease (AD). One of the most significant barriers in understanding the role of TDP-43 in neurodegeneration and developing effective treatments is the lack of reliable biomarkers that predict or report TDP-43 pathology in living FTLD and AD patients. The relationships among clinical phenotypes, local neurodegeneration, and TDP-43 pathology are not well understood. The objective of this study is to characterize a recently developed antibody to track a new biomarker. This grant proposes a variety of focused experiments to investigate the validity of the new antibody. These experiments are focused on several important and unanswered biological questions with detailed, informed, and targeted experimentation. The key component is that they lack is a discovery-based characterization of the TDP species recognized by the new antibody. My contribution to this grant is to share my expertise and instrumentation to determine the for of TDP that is recognized by this new antibody with biochemical approaches and proteomic mass spectrometry-based analysis